Biochemical studies of a patient with ketoacidosis due to a deficiency of CoA transferase has resulted in the extended investigation of the role of beta-hydroxybutyrate and acetoacetate in developmental homeostasis. The recent studies are focused on the utilization of these ketone bodies by the developing rat brain. To elucidate the metabolic interrelationship between ketone bodies, carbohydrates, and amino acids, data will be obtained from experiments using dissociated primary brain cells explanted from fetal and neonatal animals, as well as from established lines of glial and neuroblastoma cells. The studies are designed to differentiate between the metabolic fate of ketone bodies in neurons and glia and in subcellular organelles such as synaptosomes and mitochondria. Also included are studies of the role of various hormones (particularly thyroid hormone) on the uptake of ketone bodies by the various cell types and their incorporation into lipids. The results of these studies will add to our understanding of metabolic compartmentations in the brain and should help clarify some of the ambiguities surrounding the production of ketone bodies. In addition, these studies should also provide for better clinical approaches to ketotic hypoglycemia and diabetes in children.